P1190: OUTCOMES BY BCL2 AND MYC EXPRESSION AND REARRANGEMENTS IN UNTREATED DIFFUSE LARGE B-CELL LYMPHOMA FROM THE POLARIX TRIAL
Authors: F. Morschhauser, Y. Jiang, F. Jardin, A. F. Herrera, L. H. Sehn, C. Herbaux, C. Flowers, T. Phillips, A. López Guillermo, C. Diefenbach, G. P. Gregory, A. Kim, A. M. Barbui, S. Balasubramanian, W. Harris, J. Hirata, J. N. Paulson, C. Lee, G. Lenz
Journal: HemaSphere (2022)

Background: Overexpression of BCL2 and MYC, and translocation of MYC, BCL2, and BCL6, are associated with poorer outcomes in patients with diffuse large B-cell lymphoma (DLBCL; Horn et al. Blood 2013). We previously reported progression-free survival (PFS) from POLARIX in subgroups of patients with DLBCL receiving Pola-R-CHP or R-CHOP, including patients with double expressor lymphoma (DEL; favoring Pola-R-CHP: hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.42–0.97), and double- or triple-hit lymphoma (DHL/THL; favoring R-CHOP: HR 3.81, 95% CI 0.82–17.64) (Tilly et al. NEJM 2022). Aims: This is a prespecified exploratory analysis, to further analyze immunohistochemistry (IHC) expression status of BCL2 and MYC, and rearrangements (R) of BCL2, BCL6 and MYC as independent prognostic markers. The prognostic impact of DEL, and BCL2 and MYC overexpression within treatment arms was also explored. Methods: BCL2 and MYC protein expression were assessed by IHC and identified as IHC+ (≥50% [BCL2]/≥40% [MYC]) or IHC−; MYC-R, BCL2-R, and BCL6-R were detected by fluorescence in situ hybridization (Tilly et al. NEJM 2022). All patients provided informed consent. Pola-R-CHP is an investigational combination. Exploratory multivariate Cox regression models were adjusted for treatment, stratification factors (International Prognostic Index, bulky disease, geographic region), age >60 years, cell of origin, and biomarker evaluated, as appropriate. Results: The prevalence, univariate HR, and 2-year PFS estimates of BCL2+/MYC+ and BCL2-R/MYC-R/BCL6-R subgroups are presented (Table) except for BCL6-R, because all four PFS events in this subgroup were with Pola-R-CHP. Multivariate analyses results for Pola-R-CHP vs R-CHOP in patients with BCL2+ (HR 0.60, 95% CI 0.43–0.86) and those with MYC+ (HR 0.63, 95% CI 0.45–0.89) were similar to results of univariate analyses. Multivariate analyses of other subgroups were not performed due to the low patient number with BCL2-R/MYC-R/BCL6-R. While patients with DEL treated with Pola-R-CHP had improved PFS vs patients treated with R-CHOP (HR 0.64, 95% CI 0.42–0.97), the prognostic impact of DEL vs non-DEL was identified in the R-CHOP arm (univariate HR 1.53, 95% CI 1.06–2.21; multivariate HR 1.29, 95% CI 0.88–1.91) vs the Pola-R-CHP arm (univariate HR 1.10, 95% CI 0.72–1.69; multivariate HR 1.42, 95% CI 0.89–2.28). Similarly, patients with BCL2+ had inferior PFS vs patients with BCL2– in the R-CHOP arm (univariate HR 1.96, 95% CI 1.31–2.93; multivariate HR 1.74, 95% CI 1.14–2.66); however, no prognostic difference was detected in the Pola-R-CHP arm (univariate HR 1.30, 95% CI 0.85–2.01; multivariate HR 1.56, 95% CI 0.99–2.47). No prognostic impact of MYC+ vs MYC– was detected in either arm (R-CHOP: univariate HR 1.17, 95% CI 0.77–1.77; multivariate HR 1.00, 95% CI 0.65–1.55; Pola-R-CHP: univariate HR 0.83, 95% CI 0.54–1.27; multivariate HR 0.91, 95% CI 0.58–1.42). Image:Summary/Conclusion: Multivariate analyses support the benefit of Pola-R-CHP in patients with BCL2+ and MYC+ DLBCL. The poor prognostic impact associated with DEL, which was mainly driven by BCL2+, appears reduced in Pola-R-CHP- vs R-CHOP-treated patients.